Inflammation and Immune Markers in Mood Disorders

Mood disorders such as major depressive disorder and bipolar disorder are increasingly recognised as having an inflammatory component alongside classical neurotransmitter dysregulation. A growing body of evidence indicates that systemic and central immune activation, reflected in elevated levels of proinflammatory cytokines, acute‐phase proteins and altered leukocyte subsets, contributes to symptom severity, treatment response and long-term prognosis. Peripheral markers—including C-reactive protein, interleukin-6 and ratios between neutrophils, lymphocytes, monocytes and platelets—offer minimally invasive windows into the neuroimmune axis. These biomarkers correlate with clinical phenotypes such as melancholic versus atypical depression, manic versus depressive episodes in bipolar disorder and vulnerability to suicidality. Mechanistic studies implicate microglial priming, blood–brain barrier disruption and modulation of monoaminergic systems as key mediators of immune-driven mood disturbance. Moreover, metabolic factors such as obesity or dyslipidaemia may amplify inflammatory signalling, creating a bidirectional link between systemic health and psychiatric outcome. Understanding these pathways opens new avenues for personalised interventions, including anti-inflammatory adjuvants and lifestyle modification, and may help stratify patients who stand to benefit from immunomodulatory therapies.

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Inflammation and Immune Markers in Mood Disorders publication trend

The graph below shows the total number of articles in inflammation and immune markers in mood disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Neutrophil-to-lymphocyte ratio (NLR): The quotient of absolute neutrophil count divided by lymphocyte count, used as an indicator of systemic inflammation.

Platelet-to-lymphocyte ratio (PLR): The ratio of platelet count to lymphocyte count, reflecting both haemostatic and inflammatory processes.

Monocyte-to-lymphocyte ratio (MLR): The proportion of monocytes relative to lymphocytes, indicative of monocyte-driven immune activation.

C-reactive protein (CRP): An acute-phase protein produced by the liver in response to interleukin-6, serving as a sensitive marker of systemic inflammation.

Systemic immune-inflammation index (SII): A composite metric calculated as platelet count × neutrophil count / lymphocyte count, integrating multiple blood cell lines to gauge inflammatory status.

References

1. Being overweight and obese increases suicide risk, the severity of depression, and the inflammatory response in adolescents with major depressive disorders. Frontiers in Immunology (2023).
2. Neuroinflammation and psychiatric illness. Journal of Neuroinflammation (2013).
3. Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior. European Psychiatry (2020).
4. Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder. Frontiers in Psychiatry (2022).
5. Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte and Monocyte-to-Lymphocyte Ratio in Bipolar Disorder. Brain Sciences (2021).
6. Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Monocyte-to-Lymphocyte Ratio in Depression: An Updated Systematic Review and Meta-Analysis. Frontiers in Psychiatry (2022).
7. Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics. Frontiers in Psychiatry (2017).